What blood investigations are needed for a child with failure to thrive and chronic diarrhea?

Blood Investigations for Child with Failure to Thrive and Chronic Diarrhea

Begin with a focused panel of screening blood tests to exclude common treatable causes including celiac disease, anemia, and malabsorption, while avoiding extensive laboratory evaluation unless specific clinical features suggest organic disease. 1, 2

Initial Screening Blood Tests (First-Line)

Complete Blood Count (CBC) with Differential

• Assess for anemia (iron deficiency from malabsorption or chronic blood loss) 1
• Evaluate for thrombocytopenia and leukopenia (seen in storage diseases like ASMD) 1
• Check for eosinophilia (suggests food protein-induced enterocolitis syndrome or parasitic infection) 1
• Identify thrombocytosis (reported in 65% of acute FPIES cases) 1

Celiac Disease Serology

• Tissue transglutaminase IgA (TG2-IgA) is the primary screening test with 98-100% accuracy when malabsorption symptoms including failure-to-thrive are present 1
• Total IgA level must be measured simultaneously to exclude IgA deficiency (which would cause false-negative TG2-IgA) 1
• If IgA deficient, obtain IgG-based tests (deamidated gliadin peptide IgG or TG2-IgG) 1

Basic Metabolic Panel

• Serum sodium and electrolytes to detect hypernatremic dehydration or metabolic acidosis 1
• Blood glucose to exclude hyperglycemia with osmotic diuresis 1

Liver Function Tests

• Elevated transaminases occur in celiac disease, ASMD, and other storage disorders 1
• Albumin level assesses for hypoalbuminemia from protein-losing enteropathy 1

Additional First-Line Tests Based on Clinical Context

• Thyroid function tests (TSH, free T4) if autoimmune thyroid disease suspected, as celiac disease co-occurs with autoimmune conditions 1
• Fasting lipid panel if hepatosplenomegaly present (dyslipidemia with decreased HDL and increased triglycerides suggests ASMD) 1

Second-Line Blood Tests (When First-Line Normal but Symptoms Persist)

Stool Studies Should Precede Additional Blood Work

• Stool culture for bacterial pathogens (Campylobacter, Salmonella, Shigella) as chronic Campylobacter can cause failure to thrive 3
• Fecal calprotectin to exclude inflammatory bowel disease 1
• Fecal elastase for pancreatic insufficiency 1

If Malabsorption Suspected Despite Normal Initial Tests

• Fat-soluble vitamin levels (A, D, E, K) indicate fat malabsorption 1
• Prothrombin time/INR (vitamin K deficiency from malabsorption) 1
• Iron studies, ferritin, B12, and folate (deficiencies suggest small bowel disease) 1

If Storage Disease or Metabolic Disorder Suspected

• Enzyme assay for acid sphingomyelinase (ASM) activity if hepatosplenomegaly, dyslipidemia, and chronic diarrhea present 1
• Consider genetic testing early if congenital diarrhea and enteropathy (CODE) suspected, as whole-exome sequencing can expedite diagnosis 4

Critical Clinical Caveats

Avoid Extensive Laboratory Evaluation in Most Cases

• Laboratory testing yields positive results in only 3.2% of children with failure to thrive in gastroenterology clinics 2
• 89% of children with failure to thrive have nonorganic etiologies requiring behavioral and nutritional interventions rather than extensive testing 2
• The majority of children (56.4%) undergo laboratory evaluation, but this should be judiciously performed based on specific clinical indicators 2

Red Flags Requiring Expanded Workup

• Bloody diarrhea with mucus suggests invasive bacterial infection requiring immediate stool culture 5, 6
• Hepatosplenomegaly with chronic diarrhea at 6 months warrants evaluation for storage diseases (ASMD) with enzyme assays and genetic testing 1
• Persistent symptoms despite adequate caloric intake and behavioral interventions justify second-line testing 2
• Eastern European Jewish ancestry with hepatosplenomegaly should prompt early ASM enzyme assay 1

Age-Specific Considerations

• Infants under 2 years with chronic diarrhea: prioritize celiac serology, stool studies for infection, and consider food protein-induced enterocolitis syndrome 1, 4
• Normal infants may shift to lower growth percentiles in first 2 years without representing true failure to thrive 7
• Premature infants and those with Down syndrome follow different growth patterns and should not be diagnosed with failure to thrive based on standard curves alone 7

When to Consider Genetic Testing Early

• Diarrhea from birth with severe malabsorption unresponsive to dietary modifications suggests congenital enteropathy requiring whole-exome or genome sequencing 4, 8
• Consanguineous parents or affected siblings increase likelihood of genetic disorder 8
• Villus atrophy with crypt hypoplasia on biopsy without inflammatory infiltrate suggests familial enteropathy 8